This proposal concerns the genetics, structure and expression of human tubulin genes. These genes encode the Alpha- and Beta-subunits of microtubules, structures that perform an essential role in many vital organelles--cilia, flagella, the mitotic spindle and the cytoskeleton--of all eucaryotic cells. The importance of such studies lies in the possible involvement of abnormal microtubule function in association with human disease states such as the Duchenne form of muscular dystrophy, Alzheimer's disease, Leish-Nyhan Syndrome and Chediak-Higashi Syndrome. The proposed approach will involve 1) Analysis of the tubulin gene repertoire of normal and diseased individuals by Southern Blot analysis using cloned Alpha- and Beta-tubulin probes in order to explore the association of disease states with a given tubulin haplotype; 2) Identification of the chromosomal location of tubulin genes by analysis of restriction digests of genomic DNA from mouse/human hybrid cell lines containing a limited subset of human chromosomes; 3) Sequence analysis of human Alpha- and Beta-tubulin genes already shown to be incapable of yielding a functional transcript; 4) Studies on the expression of Alpha- and Beta-tubulin genes a) in vivo with respect to i) the cell cycle, ii) various differentiated cell types and iii) the extent of polymerization/depolymerization of microtubules, and b) in vitro in cell-free extracts; 5) Construction of cDNA clones containing sequences specific for tau protein.